PRKAG3

protein kinase AMP-activated non-catalytic subunit gamma 3

Basic information

Region (hg38): 2:218822307-218832086

Links

ENSG00000115592 ∙ NCBI:53632 ∙ OMIM:604976 ∙ HGNC:9387 ∙ Uniprot:Q9UGI9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Increased glyogen content in skeletal muscle	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	17878938

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRKAG3 gene.

• Inborn genetic diseases (26 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKAG3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			25	2		27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	4	2

Variants in PRKAG3

This is a list of pathogenic ClinVar variants found in the PRKAG3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-218823779-C-T		PRKAG3-related disorder	Benign (Nov 06, 2019)
2-218823787-G-A		PRKAG3-related disorder	Benign (Nov 25, 2019)
2-218823800-C-T		not specified	Uncertain significance (Mar 29, 2022)
2-218823806-C-G		not specified	Uncertain significance (Mar 20, 2023)
2-218823818-C-T		not specified	Uncertain significance (Jan 02, 2024)
2-218823845-G-A		not specified	Uncertain significance (Mar 08, 2024)
2-218823859-A-G		not specified	Uncertain significance (Dec 08, 2023)
2-218824230-G-A		not specified	Uncertain significance (Sep 15, 2021)
2-218824242-C-T		not specified	Uncertain significance (Jan 09, 2024)
2-218824243-G-A		PRKAG3-related disorder	Benign (Nov 11, 2019)
2-218824361-G-A		not specified	Uncertain significance (Nov 18, 2022)
2-218824553-G-A		not specified	Uncertain significance (Jan 17, 2024)
2-218824568-C-T		not specified	Uncertain significance (Dec 19, 2022)
2-218826934-C-T		not specified	Uncertain significance (Mar 17, 2023)
2-218826970-C-T		not specified	Uncertain significance (Sep 16, 2021)
2-218827060-G-A		not specified	Uncertain significance (Mar 01, 2023)
2-218827072-A-C		not specified	Uncertain significance (Dec 01, 2022)
2-218827077-C-T		Increased muscle glycogen content	Uncertain significance (Jun 27, 2013)
2-218827079-G-A		PRKAG3-related disorder	Likely benign (Jun 30, 2023)
2-218827089-G-A			Likely benign (Dec 31, 2019)
2-218827272-C-T		not specified	Uncertain significance (Aug 04, 2023)
2-218827310-C-T			Likely benign (Oct 01, 2022)
2-218827311-G-A		not specified	Uncertain significance (Mar 21, 2023)
2-218827330-G-A		Increased muscle glycogen content	Uncertain significance (Jun 27, 2013)
2-218827579-C-A		not specified	Uncertain significance (Dec 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRKAG3	protein_coding	protein_coding	ENST00000529249	13	9704

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.62e-12	0.188	125484	0	264	125748	0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.268	295	282	1.04	0.0000175	3139
Missense in Polyphen		101	101.42	0.99583		1163
Synonymous	-0.0535	115	114	1.01	0.00000684	1017
Loss of Function	0.829	20	24.4	0.819	0.00000115	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000797	0.000785
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000371	0.000369
Middle Eastern	0.000218	0.000217
South Asian	0.00612	0.00613
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive. {ECO:0000269|PubMed:14722619}.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Circadian rhythm - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Tight junction - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;AMP-activated Protein Kinase (AMPK) Signaling;Target Of Rapamycin (TOR) Signaling;Energy Metabolism;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Angiopoietin Like Protein 8 Regulatory Pathway;Lipid Metabolism Pathway;Liver steatosis AOP;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;Membrane Trafficking;Generic Transcription Pathway;RNA Polymerase II Transcription;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;insulin Mam;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;Mitochondrial biogenesis;Translocation of GLUT4 to the plasma membrane;VEGF;insulin;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.152

Intolerance Scores

• loftool: 0.163
• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.64

Haploinsufficiency Scores

• pHI: 0.219
• hipred: N
• hipred_score: 0.316
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prkag3
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: glycogen biosynthetic process;glycolytic process;protein phosphorylation;fatty acid biosynthetic process;cell cycle arrest;response to muscle activity involved in regulation of muscle adaptation;macroautophagy;intracellular signal transduction;regulation of protein serine/threonine kinase activity
• Cellular component: extracellular space;nucleoplasm;cytosol;nucleotide-activated protein kinase complex
• Molecular function: AMP-activated protein kinase activity;ATP binding;protein kinase binding